基于外泌体介导的巨噬细胞极化探讨针刺治疗慢性阻塞性肺疾病的潜在机制

刘路; 齐文川; 曾倩; 周子扬; 陈道鸿; 高蕾; 何斌; 蔡定均; 余曙光; 赵凌

doi:10.14148/j.issn.1672-0482.2023.0093

基于外泌体介导的巨噬细胞极化探讨针刺治疗慢性阻塞性肺疾病的潜在机制

doi: 10.14148/j.issn.1672-0482.2023.0093

刘路^1,,
齐文川¹,
曾倩¹,
周子扬¹,
陈道鸿¹,
高蕾¹,
何斌¹,
蔡定均¹,
余曙光¹,
赵凌^{1, 2, ,}

1.
成都中医药大学针灸推拿学院, 四川成都 610075
2.
四川省针灸与时间生物学重点实验室, 四川成都 610075

基金项目:

国家中医药管理局中医药创新团队及人才支持计划项目 ZYYCXTD-D-202003

四川省教育厅中央引导地方科技发展资金项目 21ZYKJCX0008

详细信息

作者简介:
刘路, 女, 博士研究生，E-mail：liulu@stu.cdutcm.edu.cn

通讯作者:
赵凌, 女，研究员，博士生导师，主要从事针刺辅助慢性病康复的临床评价及生物学基础研究，E-mail：zhaoling@cdutcm.edu.cn

中图分类号: R285.5
计量
- 文章访问数: 238
- HTML全文浏览量: 39
- PDF下载量: 17
- 被引次数: 0
出版历程
- 收稿日期: 2022-08-18
- 网络出版日期: 2023-01-18
- 发布日期: 2023-01-10

Potential Mechanism of Acupuncture Treatment for Chronic Obstructive Pulmonary Disease Based on Exosome-Mediated Macrophage Polarization

1.
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
2.
Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu 610075, China

摘要

摘要: 慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)以肺结构退行性病变、炎症和纤维化为特征, 是危害人类健康的重要呼吸系统疾病。与服用药物相比, 针刺能够改善呼吸困难, 提高患者的运动耐力以及机体免疫力且副作用较小, 但其作用机制尚不明确。炎症机制在COPD的发生中十分重要, 其中巨噬细胞是重要的炎症参与者，巨噬细胞极化在COPD的发病过程中具有关键作用。外泌体为可由多种细胞分泌的纳米级双层膜囊泡, 能够介导细胞间或器官间通讯, 调节细胞功能或细胞活动。据报道外泌体参与巨噬细胞极化, 具有调节炎症的作用。在影响COPD发生发展的机制研究中, 外泌体作为重要的突破点已受到越来越多的关注。因此主要从外泌体参与巨噬细胞极化角度出发, 阐释COPD的发病机制以及分析针刺通过调控外泌体, 参与巨噬细胞极化, 从而治疗COPD的可行性。
- 针刺 /
- 外泌体 /
- COPD /
- 巨噬细胞极化 /
- 炎症机制
Abstract: Chronic obstructive pulmonary disease (COPD) is an important respiratory disease that endangers human health, characterized by degenerative changes, inflammation and fibrosis of lung structure. Compared with taking medicine, acupuncture can improve dyspnea, exercise endurance and immunity of patients with less side effects, but its mechanism is not clear. Inflammatory mechanisms play an important role in the development of COPD, in which macrophages are important inflammatory participants. Macrophages are highly plastic and can polarize into M1-type macrophages and M2-type macrophages when stimulated by the microenvironment. After activation, M1 macrophages can release pro-inflammatory cytokines and have pro-inflammatory effects. M2 macrophages have anti-inflammatory and immunomodulatory functions. Macrophage polarization plays a key role in the pathogenesis of COPD. Exosomes are nanoscale double-membrane vesicles that can be secreted by a variety of cells, which can mediate intercellular or interorgan communication, regulate cell function or cell activity. Exosomes have been reported to be involved in macrophage polarization and have a role in regulating inflammation. As an important breakthrough, exosomes have attracted more and more attention in mechanism study of the development of COPD. Therefore, from the point of view of exosomes participating in macrophage polarization, our study explain the pathogenesis of COPD and analyzes the feasibility of acupuncture in the treatment of COPD by regulating exosomes which participants in macrophage polarization.
- acupuncture /
- exosomes /
- COPD /
- macrophage polarization /
- inflammatory mechanism

HTML全文

图 1 针刺可能通过调控外泌体参与巨噬细胞极化过程治疗COPD

Figure 1. Acupuncture's possible therapeutic mechanism in COPD treatment may be involved in macrophage polarization through modulating exosomes

下载: 全尺寸图片幻灯片

图 2 从外泌体-巨噬细胞极化角度研究针刺治疗COPD的潜在机制

Figure 2. Investigation of the potential mechanism of acupuncture in treating COPD from the perspective of exosomes-macrophage polarization

下载: 全尺寸图片幻灯片

参考文献(75)

[1]	李建生. 国际中医临床实践指南: 慢性阻塞性肺疾病[J]. 世界中医药, 2020, 15(7): 1084-1092. doi: 10.3969/j.issn.1673-7202.2020.07.026 LI JS. International clinical practice guideline of Chinese medicine chronic obstructive pulmonary disease[J]. World Chin Med, 2020, 15(7): 1084-1092. doi: 10.3969/j.issn.1673-7202.2020.07.026
[2]	ROH JA, KIM KI, PARK J, et al. The efficacy of manual therapy (Chuna) for chronic obstructive pulmonary disease: Protocol for a systematic review[J]. Medicine, 2020, 99(9): e18832. doi: 10.1097/MD.0000000000018832
[3]	陈亚红. 2021年GOLD慢性阻塞性肺疾病诊断、治疗及预防全球策略解读[J]. 中国医学前沿杂志(电子版), 2021, 13(1): 16-37. https://www.cnki.com.cn/Article/CJFDTOTAL-YXQY202101002.htm CHEN YH. Interpretation of global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2021 report[J]. Chin J Front Med Sci Electron Version, 2021, 13(1): 16-37. https://www.cnki.com.cn/Article/CJFDTOTAL-YXQY202101002.htm
[4]	WANG C, XU JY, YANG L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health[CPH]study): A national cross-sectional study[J]. Lancet, 2018, 391(10131): 1706-1717. doi: 10.1016/S0140-6736(18)30841-9
[5]	NAGHAVI M, ABAJOBIR AA, ABBAFATI C, et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: A systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet, 2017, 390(10100): 1151-1210. doi: 10.1016/S0140-6736(17)32152-9
[6]	ZHOU MG, WANG HD, ZENG XY, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2019, 394(10204): 1145-1158. doi: 10.1016/S0140-6736(19)30427-1
[7]	BAGDONAS E, RAUDONIUTE J, BRUZAUSKAITE I, et al. Novel aspects of pathogenesis and regeneration mechanisms in COPD[J]. Int J Chron Obstruct Pulmon Dis, 2015, 10: 995-1013.
[8]	BARNES PJ. COPD 2020: New directions needed[J]. Am J Physiol Lung Cell Mol Physiol, 2020, 319(5): L884-L886. doi: 10.1152/ajplung.00473.2020
[9]	HE SY, CHEN DN, HU MY, et al. Bronchial epithelial cell extracellular vesicles ameliorate epithelial-mesenchymal transition in COPD pathogenesis by alleviating M2 macrophage polarization[J]. Nanomed Nanotechnol Biol Med, 2019, 18: 259-271. doi: 10.1016/j.nano.2019.03.010
[10]	WANG LJ, CHEN Q, YU Q, et al. Cigarette smoke extract-treated airway epithelial cells-derived exosomes promote M1 macrophage polarization in chronic obstructive pulmonary disease[J]. Int Immunopharmacol, 2021, 96: 107700. doi: 10.1016/j.intimp.2021.107700
[11]	LABAKI WW, ROSENBERG SR. Chronic obstructive pulmonary disease[J]. Ann Intern Med, 2020, 173(3): ITC17-ITC32. doi: 10.7326/AITC202008040
[12]	李正欢, 张晓云, 陈杨, 等. 2020年慢性阻塞性肺疾病全球倡议《COPD诊断、治疗与预防全球策略》指南解读(一): 稳定期药物管理[J]. 中国全科医学, 2021, 24(8): 923-929. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202108022.htm LI ZH, ZHANG XY, CHEN Y, et al. Interpretation of the 2020 GOLD's global strategy for Prevention, diagnosis and management of COPD(Ⅰ): Pharmacological treatment of stable COPD[J]. Chin Gen Pract, 2021, 24(8): 923-929. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202108022.htm
[13]	李尹, 张新芳, 刘自兵, 等. 电针对慢性阻塞性肺疾病大鼠肺泡巨噬细胞M1极化的影响[J]. 针刺研究, 2020, 45(3): 173-179. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ202003002.htm LI Y, ZHANG XF, LIU ZB, et al. Effect of electroacupuncture on pulmonary function and M1 polarization of alveolar macrophages in rats with chronic obstructive pulmonary disease[J]. Acupunct Res, 2020, 45(3): 173-179. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ202003002.htm
[14]	CHEN B, LI MY, GUO Y, et al. Mast cell-derived exosomes at the stimulated acupoints activating the neuro-immune regulation[J]. Chin J Integr Med, 2017, 23(11): 878-880. doi: 10.1007/s11655-016-2269-8
[15]	HUANG Y, YU MS, KUMA A, et al. Downregulation of let-7 by electrical acupuncture increases protein synthesis in mice[J]. Front Physiol, 2021, 12: 697139. doi: 10.3389/fphys.2021.697139
[16]	ZOU Y, BHAT OM, YUAN XX, et al. Release and actions of inflammatory exosomes in pulmonary emphysema: Potential therapeutic target of acupuncture[J]. J Inflamm Res, 2021, 14: 3501-3521. doi: 10.2147/JIR.S312385
[17]	周琦, 孙慧娟, 于栋华, 等. 巨噬细胞M1/M2型极化在不同疾病中的作用机制[J]. 中国药理学通报, 2020, 36(11): 1502-1506. doi: 10.3969/j.issn.1001-1978.2020.11.005 ZHOU Q, SUN HJ, YU DH, et al. Mechanisms of M1/M2 macrophage polarization in different diseases[J]. Chin Pharmacol Bull, 2020, 36(11): 1502-1506. doi: 10.3969/j.issn.1001-1978.2020.11.005
[18]	ARORA S, DEV K, AGARWAL B, et al. Macrophages: Their role, activation and polarization in pulmonary diseases[J]. Immunobiology, 2018, 223(4/5): 383-396.
[19]	贾瑞, 惠毅, 闫曙光, 等. 巨噬细胞M1/M2型极化与免疫炎症性疾病关系的研究进展[J]. 中国免疫学杂志, 2021, 37(22): 2791-2797. doi: 10.3969/j.issn.1000-484X.2021.22.019 JIA R, HUI Y, YAN SG, et al. Research progress on relationship between macrophage M1/M2 polarization and immune inflammatory diseases[J]. Chin J Immunol, 2021, 37(22): 2791-2797. doi: 10.3969/j.issn.1000-484X.2021.22.019
[20]	GENIN M, CLEMENT F, FATTACCIOLI A, et al. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide[J]. BMC Cancer, 2015, 15: 577. doi: 10.1186/s12885-015-1546-9
[21]	王青青, 荣令. COPD中炎性细胞及分子机制的研究进展[J]. 临床肺科杂志, 2019, 24(12): 2258-2262. doi: 10.3969/j.issn.1009-6663.2019.12.029 WANG QQ, RONG L. Research progress of inflammatory cells and molecular mechanism in COPD[J]. J Clin Pulm Med, 2019, 24(12): 2258-2262. doi: 10.3969/j.issn.1009-6663.2019.12.029
[22]	PESCI A, BALBI B, MAJORI M, et al. Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease[J]. Eur Respir J, 1998, 12(2): 380-386. doi: 10.1183/09031936.98.12020380
[23]	KEATINGS VM, COLLINS PD, SCOTT DM, et al. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma[J]. Am J Respir Crit Care Med, 1996, 153(2): 530-534. doi: 10.1164/ajrccm.153.2.8564092
[24]	BECKETT EL, STEVENS RL, JARNICKI AG, et al. A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis[J]. J Allergy Clin Immunol, 2013, 131(3): 752-762. e7. doi: 10.1016/j.jaci.2012.11.053
[25]	BAZZAN E, TURATO G, TINè M, et al. Dual polarization of human alveolar macrophages progressively increases with smoking and COPD severity[J]. Respir Res, 2017, 18(1): 40. doi: 10.1186/s12931-017-0522-0
[26]	LI NN, LIU Y, CAI JF. LncRNA MIR155HG regulates M1/M2 macrophage polarization in chronic obstructive pulmonary disease[J]. Biomed Pharmacother, 2019, 117: 109015. doi: 10.1016/j.biopha.2019.109015
[27]	HE S, XIE L, LU J, et al. Characteristics and potential role of M2 macrophages in COPD[J]. Int J Chron Obstruct Pulmon Dis, 2017, 12: 3029-3039. doi: 10.2147/COPD.S147144
[28]	陈兴无, 邢敏, 秦立龙, 等. 气道上皮细胞对巨噬细胞表型和吞噬功能的影响及HIF-1α的作用[J]. 中国病理生理杂志, 2019, 35(1): 141-149. doi: 10.3969/j.issn.1000-4718.2019.01.022 CHEN XW, XING M, QIN LL, et al. Effects of airway epithelial cells on phenotype and phagocytosis of macrophages and roles of HIF-1α[J]. Chin J Pathophysiol, 2019, 35(1): 141-149. doi: 10.3969/j.issn.1000-4718.2019.01.022
[29]	李尹, 鲁静, 张毅, 等. 巨噬细胞极化及其在慢性阻塞性肺疾病中的作用[J]. 生理学报, 2019, 71(4): 604-612. https://www.cnki.com.cn/Article/CJFDTOTAL-SLXU201904012.htm LI Y, LU J, ZHANG Y, et al. Macrophages polarization and their role in chronic obstructive pulmonary disease[J]. Acta Physiol Sin, 2019, 71(4): 604-612. https://www.cnki.com.cn/Article/CJFDTOTAL-SLXU201904012.htm
[30]	LIU L, QIN YQ, CAI ZH, et al. Effective-components combination improves airway remodeling in COPD rats by suppressing M2 macrophage polarization via the inhibition of mTORC2 activity[J]. Phytomedicine, 2021, 92: 153759. doi: 10.1016/j.phymed.2021.153759
[31]	BARUAH J, WARY KK. Exosomes in the regulation of vascular endothelial cell regeneration[J]. Front Cell Dev Biol, 2019, 7: 353.
[32]	WANG YL, LIU LC, HUNG Y, et al. Long non-coding RNA HOTAIR in circulatory exosomes is correlated with ErbB2/HER2 positivity in breast cancer[J]. Breast, 2019, 46: 64-69. doi: 10.1016/j.breast.2019.05.003
[33]	HEO J, KANG H. Exosome-based treatment for atherosclerosis[J]. Int J Mol Sci, 2022, 23(2): 1002. doi: 10.3390/ijms23021002
[34]	CHAN BD, WONG WY, LEE MML, et al. Exosomes in inflammation and inflammatory disease[J]. Proteomics, 2019, 19(8): e1800149. doi: 10.1002/pmic.201800149
[35]	CHENG XF, ZHANG GY, ZHANG L, et al. Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration[J]. J Cell Mol Med, 2018, 22(1): 261-276. doi: 10.1111/jcmm.13316
[36]	GOMEZ-CABRERO D, MENCHE J, VARGAS C, et al. From comorbidities of chronic obstructive pulmonary disease to identification of shared molecular mechanisms by data integration[J]. BMC Bioinform, 2016, 17(15): 441.
[37]	HOBBS BD, HERSH CP. Integrative genomics of chronic obstructive pulmonary disease[J]. Biochem Biophys Res Commun, 2014, 452(2): 276-286. doi: 10.1016/j.bbrc.2014.07.086
[38]	WAHLUND CJE, EKLUND A, GRUNEWALD J, et al. Pulmonary extracellular vesicles as mediators of local and systemic inflammation[J]. Front Cell Dev Biol, 2017, 5: 39. doi: 10.3389/fcell.2017.00039
[39]	XU H, LING M, XUE JC, et al. Exosomal microRNA-21 derived from bronchial epithelial cells is involved in aberrant epithelium-fibroblast cross-talk in COPD induced by cigarette smoking[J]. Theranostics, 2018, 8(19): 5419-5433. doi: 10.7150/thno.27876
[40]	GUIOT J, STRUMAN I, LOUIS E, et al. Exosomal miRNAs in lung diseases: From biologic function to therapeutic targets[J]. J Clin Med, 2019, 8(9): 1345. doi: 10.3390/jcm8091345
[41]	LEE H, ZHANG D, ZHU ZW, et al. Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs[J]. Sci Rep, 2016, 6: 35250. doi: 10.1038/srep35250
[42]	LEE H, ABSTON E, ZHANG D, et al. Extracellular vesicle: An emerging mediator of intercellular crosstalk in lung inflammation and injury[J]. Front Immunol, 2018, 9: 924. doi: 10.3389/fimmu.2018.00924
[43]	CHEN Z, WU H, SHI R, et al. miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization[J]. Biochem Biophys Res Commun, 2021, 572: 157-163. doi: 10.1016/j.bbrc.2021.07.093
[44]	FENG HS, YIN Y, REN Y, et al. Effect of CSE on M1/M2 polarization in alveolar and peritoneal macrophages at different concentrations and exposure in vitro[J]. In Vitro Cell Dev Biol-Animal, 2020, 56(2): 154-164. doi: 10.1007/s11626-019-00426-4
[45]	ISMAIL N, WANG Y, DAKHLALLAH D, et al. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer[J]. Blood, 2013, 121(6): 984-995.
[46]	LEE H, ZHANG D, WU JX, et al. Lung epithelial cell-derived microvesicles regulate macrophage migration via microRNA-17/221-induced integrin β₁ recycling[J]. J Immunol, 2017, 199(4): 1453-1464. doi: 10.4049/jimmunol.1700165
[47]	HOUGH KP, CHANDA D, DUNCAN SR, et al. Exosomes in immunoregulation of chronic lung diseases[J]. Allergy, 2017, 72(4): 534-544. doi: 10.1111/all.13086
[48]	代利利, 李秋芬, 倪光夏. 针刺五脏俞治疗慢性阻塞性肺疾病合并焦虑、抑郁临床观察[J]. 辽宁中医杂志, 2020, 47(12): 151-153. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY202012046.htm DAI LL, LI QF, NI GX. Observation of clinical effect of acupuncture on five-Zang back Shu points for treating COPD complicated with anxiety or depression[J]. Liaoning J Tradit Chin Med, 2020, 47(12): 151-153. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY202012046.htm
[49]	陈年环. 针刺治疗慢性阻塞性肺疾病稳定期的临床疗效及对患者肺功能、健康状况的影响[J]. 河北中医, 2018, 40(3): 434-437. doi: 10.3969/j.issn.1002-2619.2018.03.026 CHEN NH. Clinical efficacy of acupuncture in treating stable chronic obstructive pulmonary disease and its influence on patients' lung function and health status[J]. Hebei J Tradit Chin Med, 2018, 40(3): 434-437. doi: 10.3969/j.issn.1002-2619.2018.03.026
[50]	何颖, 李桂元, 郑则广, 等. 电针对稳定期慢性阻塞性肺疾病患者小气道功能的影响[J]. 中国针灸, 2021, 41(8): 861-865, 875. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZE202108008.htm HE Y, LI GY, ZHENG ZG, et al. Effect of electroacupuncture on small airway function in patients with stable chronic obstructive pulmonary disease[J]. Chin Acupunct Moxibust, 2021, 41(8): 861-865, 875. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZE202108008.htm
[51]	袁思成, 芮庆林. 针灸疗法辅助治疗慢性阻塞性肺疾病急性加重期研究进展[J]. 中国中医急症, 2020, 29(1): 165-167, 181. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJZ202001046.htm YUAN SC, RUI QL. Research progress of acupuncture and moxibustion in the treatment of acute exacerbation of chronic obstructive pulmonary disease[J]. J Emerg Tradit Chin Med, 2020, 29(1): 165-167, 181. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYJZ202001046.htm
[52]	WANG JJ, LI JS, YU XQ, et al. Acupuncture therapy for functional effects and quality of life in COPD patients: A systematic review and Meta-analysis[J]. Biomed Res Int, 2018, 2018: 3026726.
[53]	FERNÁNDEZ-JANE C, VILARO J, FEI YT, et al. Filiform needle acupuncture for copd: A systematic review and meta-analysis[J]. Complementary Ther Med, 2019, 47: 102182. doi: 10.1016/j.ctim.2019.08.016
[54]	MA JD, TIAN YG, LI JS, et al. Effect of Bufei yishen granules combined with electroacupuncture in rats with chronic obstructive pulmonary disease via the regulation of TLR-4/NF-κB signaling[J]. Evid Based Complementary Altern Med, 2019, 2019: 6708645.
[55]	官锦帅, 刘雪梅, 樊涛, 等. 针刺足三里对COPD大鼠血浆多巴胺和肺功能的影响[J]. 四川大学学报(医学版), 2019, 50(2): 203-209. https://www.cnki.com.cn/Article/CJFDTOTAL-HXYK201902011.htm GUAN JS, LIU XM, FAN T, et al. Effects of acupuncture at Zusanli on plasma dopamine and lung function of rats with COPD[J]. J Sichuan Univ Med Sci Ed, 2019, 50(2): 203-209. https://www.cnki.com.cn/Article/CJFDTOTAL-HXYK201902011.htm
[56]	GENG WY, LIU ZB, SONG NN, et al. Effects of electroacupuncture at Zusanli (ST36) on inflammatory cytokines in a rat model of smoke-induced chronic obstructive pulmonary disease[J]. J Integr Med, 2013, 11(3): 213-219.
[57]	LIU X, FAN T, FU J, et al. The relationship between nod-like receptor family pyrin domain containing 3 inflammasome and dopamine in the inflammation regulation mechanism of acupuncture for chronic obstructive pulmonary disease[J]. Am J Rrspirat Crit Care Med, 2018, 197: 1-23.
[58]	陈建飞, 罗伟贤, 周鸿飞. 不同针刺频率对稳定期慢性阻塞性肺疾病患者呼吸功能及免疫状态的影响[J]. 世界中医药, 2018, 13(11): 2839-2842. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZA201811045.htm CHEN JF, LUO WX, ZHOU HF. Effects of different acupuncture frequency on respiratory function and immune status in patients with stable chronic obstructive pulmonary disease[J]. World Chin Med, 2018, 13(11): 2839-2842. https://www.cnki.com.cn/Article/CJFDTOTAL-SJZA201811045.htm
[59]	童娟, 陈福初, 李桂元, 等. 电针对慢性阻塞性肺病肌营养不良大鼠的抗炎免疫调节作用[J]. 针刺研究, 2018, 43(4): 236-241, 246. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201804008.htm TONG J, CHEN FC, LI GY, et al. Anti-inflammatory and immunomodulatory effects of electro-chronic obstructive pulmonary disease muscular dystrophy rats[J]. Acupunct Res, 2018, 43(4): 236-241, 246. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201804008.htm
[60]	吉紫乐, 谢洋, 王艳, 等. 针刺治疗慢性阻塞性肺疾病作用机制的文献分析[J]. 中医杂志, 2021, 62(22): 2003-2010. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202122014.htm JI ZL, XIE Y, WANG Y, et al. Literature analysis on the mechanism of acupuncture in the treatment of chronic obstructive pulmonary disease[J]. J Tradit Chin Med, 2021, 62(22): 2003-2010. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZYZ202122014.htm
[61]	骆言, 黄学宽, 吴忠练, 等. 电针对慢性阻塞性肺疾病大鼠肺组织基质金属蛋白酶9及组织金属蛋白酶抑制剂1表达的影响[J]. 针刺研究, 2014, 39(5): 367-371. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201405006.htm LUO Y, HUANG XK, WU ZL, et al. Effects of electroacupuncture intervention on expression of pulmonary metalloproteinase-9 and tissue inhibitor-1 proteins in rats with chronic obstructive pulmonary disease[J]. Acupunct Res, 2014, 39(5): 367-371. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201405006.htm
[62]	ZHANG XF, ZHU J, GENG WY, et al. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease[J]. J Integr Med, 2014, 12(5): 417-424.
[63]	SONG SN, AN J, LI YL, et al. Electroacupuncture at ST-36 ameliorates DSS-induced acute colitis via regulating macrophage polarization induced by suppressing NLRP3/IL-1β and promoting Nrf2/HO-1[J]. Mol Immunol, 2019, 106: 143-152.
[64]	张思依, 胡霞, 唐宏图. 针刺对高脂饮食诱导的肥胖小鼠白色脂肪组织巨噬细胞极化的影响[J]. 中国针灸, 2017, 37(11): 1205-1211. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZE201711028.htm ZHANG SY, HU X, TANG HT. Effect of acupuncture on macrophage polarization of white adipose tissue in obese mice induced by high-fat diet[J]. Chin Acupunct Moxibust, 2017, 37(11): 1205-1211. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGZE201711028.htm
[65]	YANG FM, GONG YN, YU NN, et al. ST36 acupuncture alleviates the inflammation of adjuvant-induced arthritic rats by targeting monocyte/macrophage modulation[J]. Evid Based Complementary Altern Med, 2021, 2021: 9430501.
[66]	VAN DIEST SA, STANISOR OI, BOECKXSTAENS GE, et al. Relevance of mast cell-nerve interactions in intestinal nociception[J]. Biochim Biophys Acta BBA Mol Basis Dis, 2012, 1822(1): 74-84.
[67]	DING SS, HONG SH, WANG C, et al. Acupuncture modulates the neuro-endocrine-immune network[J]. QJM, 2013, 107(5): 341-345.
[68]	陈波, 李柠岑, 郭义, 等. Exosome在针刺信息传导中的网络调节作用探讨[J]. 辽宁中医杂志, 2019, 46(3): 605-607, 671. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY201903048.htm CHEN B, LI NC, GUO Y, et al. Exosome network adjusting action research in acupuncture information transmission[J]. Liaoning J Tradit Chin Med, 2019, 46(3): 605-607, 671. https://www.cnki.com.cn/Article/CJFDTOTAL-LNZY201903048.htm
[69]	CHEN B, LI MY, XING LY, et al. Participation of local exosomes of acupoints in the initiation of acupuncture analgesic effect[J]. World J Acupunct Moxibust, 2018, 28(4): 263-267, 312.
[70]	陈波, 李明月, 郭义, 等. 肥大细胞源性外来体参与构建针刺穴位效应启动小网络的探讨[J]. 针刺研究, 2015, 40(1): 82-85. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201501019.htm CHEN B, LI MY, GUO Y, et al. Mast cell-derived exosome participates in acupoint-stimulation initiated local network activities[J]. Acupunct Res, 2015, 40(1): 82-85. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYJ201501019.htm
[71]	刘小亚. Exosome在针灸参与自稳态调节机制中的作用探讨[J]. 现代盐化工, 2021, 48(3): 104-105, 108. https://www.cnki.com.cn/Article/CJFDTOTAL-SYKZ202103050.htm LIU XY. Discussion on the role of Exosome in acupuncture and moxibustion participating in homeostasis regulation mechanism[J]. Mod Salt Chem Ind, 2021, 48(3): 104-105, 108. https://www.cnki.com.cn/Article/CJFDTOTAL-SYKZ202103050.htm
[72]	叶静. 针刺对膝骨性关节炎患者血清外泌体microRNA的调控机制研究[D]. 成都: 成都中医药大学, 2019. YE J. Regulation mechanism of serum exosome microRNA in patients with knee osteoarthritis by acupuncture[D]. Chengdu: Chengdu Univ Chin Med, 2019.
[73]	匡泓俊, 黄文豪, 李星慧, 等. 针灸效应机制中外泌体的研究进展[J]. 山东中医药大学学报, 2021, 45(5): 707-711. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYX202105024.htm KUANG HJ, HUANG WH, LI XH, et al. Research progress of exosomes in the action mechanism of acupuncture and moxibustion[J]. J Shandong Univ Tradit Chin Med, 2021, 45(5): 707-711. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYX202105024.htm
[74]	KLEIN JD, WANG XH. Electrically stimulated acupuncture increases renal blood flow through exosome-carried miR-181[J]. Am J Physiol Renal Physiol, 2018, 315(6): F1542-F1549.
[75]	ZHANG S, JIN T, WANG L, et al. Electro-acupuncture promotes the differentiation of endogenous neural stem cells via exosomal microRNA 146b after ischemic stroke[J]. Front Cell Neurosci, 2020, 14: 223.